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Coiled-coil domain-containing 37 (FLJ40083)

From Wikipedia, the free encyclopedia

Coiled-coil domain-containing 37, also known as FLJ40083, is a protein that in humans is encoded by the CCDC37 gene (3q21.3). There is no confirmed function of CCDC37.

Gene

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Locus

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The human gene CCDC37 is found on chromosome 3 at the band 3q21.3.[1] It extends from base pairs 90,403,731 to 90,429,231, making the gene 25,500 base pairs long. It is located on the plus strand and contains 17 exons.[citation needed]

Homology

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Paralogs

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There is only one paralog for CCDC37 found in humans, CCDC38. CCDC38 is located on chromosome 12.[2]

Orthologs

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The ortholog space of CCDC37 is fairly broad including mammals, reptiles, birds, amphibians, fish, invertebrates, and fungi.[citation needed]

Genus and species Common name Class Accession Percent identity
Pan troglodytes Chimpanzee Mammalia XP_516716.3 99%
Otolemur crassicaudatus Bushbaby Mammalia 78%
Sus scrofa Pig Mammalia XP_005666178.1 70%
Felis catus Cat Mammalia XP_006929102.1 69%
Canis lupus Dog Mammalia XP_005632343.1 68%
Mus musculus Mouse Mammalia NP_776136.2 67%
Orcinus orca Killer whale Mammalia XP_004285517.1 67%
Anolis carolinensis Carolina anole Reptilia XP_003217822.1 54%
Python bivittatus Burmese python Reptilia XP_007437868.1 53%
Chrysemys picta bellii Painted turtle Reptilia XP_005288479 52%
Pseudopodoces humilis Ground tit Aves XP_005522312.1 46%
Gallus gallus Chicken Aves XP_425162.4 46%
Xenopus (Silurana) tropicalis Western clawed frog Amphibia XP_002938271.2 43%
Astyanax mexicanus Blind cave fish Actinopterygii XP_007253378.1 43%
Saccoglossus kowalevskii Acorn worm Enteropneusta XP_002742365.1 43%
Ciona intestinalis Vase tunicate Ascidiacea XP_002131495.1 43%
Aplysia californica California sea slug Gastropoda XP_005108122.1 41%
Crassostrea gigas Pacific oyster Bivalvia gbEKC37281.1 37%
Batrachochytrium dendrobatidis Amphibian chytrid fungus Chytridiomycetes XP_006680088.1 37%

Protein

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Primary sequence

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The gene encodes a protein called CCDC37. This protein in 611 amino acids in length and has a molecular weight of 71.1 kilodaltons and an isoelectric point of pI=6.7.[citation needed]

Domains

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CCDC37 contains a DUF4200 region located from amino acid 151 to 269.[1] There is no known function for DUF4200. CCDC37 also contains three coiled coil domains at amino acids 164–203, 392–436, and 526–571.[3]

Post-translational modifications

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The protein has several probable post-translational modifications. It contains four possible PEST sequence at amino acids 17–36, 293–304, 337–360, and 360–395.[4] It also contains a possible substrate of N-acetyltransferase A at Ser2.[5]

Signal peptides

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CCDC37 has a predicted nuclear localization via Reinhard's method[6] (reliability 94.1%) using a bipartite nuclear localization signal peptide starting at amino acid 155: KRQMFLLQYALDVKRRE.[7] CCDC37 also has a few predicted nuclear export signals I232, L235, I239, and M551.[8]

Expression

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CCDC37 protein is widely expressed in mus musculus but only minimally so. Most areas that express CCDC37 have an expression level of 20-40%. Expression levels in the trigeminal nerve, testis, medial olfactory epithelium, dorsal root ganglia, and trachea are the highest with almost 75% expression.[9] CCDC37 is expressed in the cerebellum, medulla, and hippocampal formation in the brain of mus musculus.[10]

Between 20 and 30 days after birth in mus musculus, CCDC37 expression increases from less than 50% to about 85%.[11]

In rattus norvegicus CCDC37 is highly expressed in oligodendrocyte progenitor cells (approximately 85%) but only narrowly expressed in oligodendrocytes themselves (~40%).[12]

Interacting proteins

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Transcription factors

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There are many predicted transcription factor binding sites in the CCDC37 promoter.[citation needed] Below is a table of the best possibilities, which have high confidence values, evolutionary conservation, and/or multiple possible binding sites in the promoter.

Transcription Factor Start End Strand Sequence
Activator-, mediator- and TBP-dependent core promoter element for RNA polymerase II transcription from TATA-less promoters 115 125 - ggGAGGgatcg
Nuclear factor 1 185 205 + tgctTGGCacgtggcgaataa
E-box binding factors 186 202 - ttcgccaCGTGccaagc
E-box binding factors 187 203 + cttggCACGtggcgaat
Vertebrate homologues of enhancer of split complex 187 201 - tcgccaCGTGccaag
Vertebrate homologues of enhancer of split complex 188 202 + ttggCACGtggcgaa
CCAAT binding factors 203 217 + taaaCCAAtcaggat
E-box binding factors 288 304 + tgggccaGGCGctgtcc
E-box binding factors 352 368 + ccggcccCGCGccctcc
Activator-, mediator- and TBP-dependent core promoter element for RNA polymerase II transcription from TATA-less promoters 353 363 - gcGCGGggccg
RNA polymerase II transcription factor II B 358 364 + ccgCGCC
cAMP-responsive element binding proteins 416 436 - tggctgTGACgccacaaaggc
SOX/SRY-sex/testis determining and related HMG box factors 438 462 + cctgaAGAAtggttgccttggagac
X-box binding factors 449 469 - ggtttacgtctccaAGGCaac
cAMP-responsive element binding proteins 452 472 - ttgggtTTACgtctccaaggc
GLI-Kruppel family member GLI3 74 88 - atcgCCACccacact
"Negative" glucocoticoid response elements 478 492 - cagctccaGGAGcag
Core promoter motif ten elements 538 558 - gaccgcgAGCGcacccaccga
GC-Box factors SP1/GC 564 580 + agagggGGCGcgcgggg
ZF5 POZ domain zinc finger 566 580 - ccccgCGCGccccct
E2F-myc activator/cell cycle regulator 566 582 + aggggGCGCgcggggtc

Interactions

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There have been three proteins found to interact by physical association with CCDC37 through a yeast two-hybrid screen: histone-lysine N-methyltransferase (SUV39H1), histone-lysine N-methyltransferase (SUV39H2), and lysine-specific histone demethylase 1A (KDM1A).[13]

Clinical significance

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In a study of the genes expressed in lung squamous cell carcinomas it was found that the promoter region of CCDC37 was hyper methylated causing down regulation of the expression of CCDC37.[14] In a separate study, CCDC37 was also found in spatial and temporal regions in mice that are associated with hereditary congenital facial paresis (HCFP) gene. However through knock out experiments in mice it was found that CCDC37 was unlikely to be a causative agent for the HCFP phenotype.[15]

References

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  1. ^ a b "CCDC37 coiled-coil domain containing 37 [Homo sapiens (human)] - Gene". Ncbi.nlm.nih.gov. Retrieved 2015-03-07.
  2. ^ "CCDC38 coiled-coil domain containing 38 [Homo sapiens (human)] - Gene". Ncbi.nlm.nih.gov. Retrieved 2015-03-07.
  3. ^ Dinkel, H. The eukaryotic linear motif resource ELM: 10 years and counting. Nucleic Acids Res. 2014 Jan;42(Database issue):D259-66.
  4. ^ "EMBOSS: epestfind". Emboss.bioinformatics.nl. Retrieved 2015-03-07.
  5. ^ Kiemer, Lars, Kyrlov Bendtsen, and Blom, Nikolai. NetAcet: Prediction of N-terminal Acetylation Sites. Bioinformatics, 2004.
  6. ^ A. Reinhardt and T. Hubbard, Nucleic Acids Res. 26, 2230, 1998
  7. ^ Dingwall C, Robbins J, Dilworth SM, Roberts B, Richardson WD (Sep 1988). "The nucleoplasmin nuclear location sequence is larger and more complex than that of SV-40 large T antigen". J. Cell Biol. 107 (3): 841–9.
  8. ^ Analysis and prediction of leucine-rich nuclear export signals Tanja la Cour, Lars Kiemer, Anne Mølgaard, Ramneek Gupta, Karen Skriver and Søren Brunak Protein Eng. Des. Sel., 17(6):527-36, 2004.
  9. ^ "4632676 - GEO Profiles - NCBI". Ncbi.nlm.nih.gov. 2014-11-12. Retrieved 2015-03-07.
  10. ^ Primary publication: Lein, E.S. et al. (2007) Genome-wide atlas of gene expression in the adult mouse brain, Nature 445: 168-176. doi: 10.1038/nature05453; and
  11. ^ "4786837 - GEO Profiles - NCBI". Ncbi.nlm.nih.gov. 2014-11-12. Retrieved 2015-03-07.
  12. ^ "31253706 - GEO Profiles - NCBI". Ncbi.nlm.nih.gov. 2014-11-12. Retrieved 2015-03-07.
  13. ^ Weimann, M. A Y2H-seq approach defines the human protein methyltransferase interactome. Nat Methods. 2013 Apr;10(4):339-42.
  14. ^ Kwon, Yong-Jae PhD; Lee, Seog Joo MSc et al. Genome-Wide Analysis of DNA Methylation and the Gene Expression Change in Lung Cancer Journal of Thoracic Oncology: January 2012 - Volume 7 - Issue 1 - pp 20-33.
  15. ^ "OMIM Entry - % 601471 - FACIAL PARESIS, HEREDITARY CONGENITAL, 1; HCFP1". Omim.org. Retrieved 2015-03-07.